Soluble Triggering Receptor Expressed on Myeloid Cells 1 in lung cancer

Andreas Kuemmel,Markus Radsak,Rainer Wiewrodt,Arik Bernard Schulze,Astrid Alflen,Martin Sebastian,Roland Buhl,Lars Henning Schmidt

doi:10.1038/s41598-018-28971-0

Abstract

Soluble Triggering Receptor Expressed on Myeloid Cells 1 (sTREM-1) can be found in the sera of patients with infectious, autoimmune and malignant diseases. The primary objective of this study was to investigate the prognostic significance of sTREM-1 in lung cancer patients. We analyzed the sera of 164 patients with lung cancer of all histologies and all stages at the time of diagnosis. We employed an ELISA using the anti-TREM-1 clone 6B1.1G12 mAb and recombinant human TREM-1. Patient data was collected retrospectively by chart review. In ROC-analysis, a sTREM-1 serum level of 163.1 pg/ml showed the highest Youden-Index. At this cut-off value sTREM-1 was a marker of short survival in patients with NSCLC (median survival 8.5 vs. 13.3 months, p = 0.04). A Cox regression model showed stage (p < 0.001) and sTREM-1 (p = 0.011) to indicate short survival. There were no differences in sTREM-1 serum values among patients with or without infection, pleural effusion or COPD. sTREM-1 was not associated with metastasis at the time of diagnosis and was not a predictor of subsequent metastasis. In SCLC patients sTREM-1 levels were lower than in NSCLC patients (p = 0.001) and did not predict survival. sTREM-1 did not correlate with CRP or the number of neutrophils. In non-small cell lung cancer patients, sTREM-1 in serum has prognostic significance.

Highlights

Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1, CD354) is an innate inflammatory transmembrane receptor first described to be expressed by neutrophils and monocytes[1]
STREM-1 has been proposed to be an accurate marker for infectious diseases such as pneumonia[12] and sepsis[13], but later on sTREM-1 in sera has been found in many non-infectious diseases like COPD14, pancreatitis[15] and inflammatory bowel disease[16]
TREM-1 is not expressed by cancer cells, but cancer cells induce the expression of TREM-1 in macrophages[21,22]

Summary

Introduction

Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1, CD354) is an innate inflammatory transmembrane receptor first described to be expressed by neutrophils and monocytes[1]. TREM-1 is believed to amplify both infectious and non-infectious inflammation[4] and to elicit the release of TNF-alpha, IL-8, myeloperoxidase and nitric oxide by innate immune cells[1]. STREM-1 has been proposed to be an accurate marker for infectious diseases such as pneumonia[12] and sepsis[13], but later on sTREM-1 in sera has been found in many non-infectious diseases like COPD14, pancreatitis[15] and inflammatory bowel disease[16]. Corresponding to the supposed anti-inflammatory role of sTREM-1 in inflammation, a study in solid malignancies including lung cancer found sTREM-1 in patients’ sera to be correlated with the absence of metastasis[25]. Contradictory to this, a doctoral thesis found sTREM-1 in sera to be correlated with short survival in lung cancer patients with pleural effusion[26]

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